Rivera Miguel A, Fahey Thomas D, López-Taylor Juan R, Martínez Juan L
Department of Physical Medicine, Rehabilitation & Sports Medicine, School of Medicine, University of Puerto Rico, Main Building Office A204, San Juan, PR, 00936, USA.
Department of Kinesiology, California State University, Chico, CA, USA.
Sports Med Open. 2020 Mar 20;6(1):16. doi: 10.1186/s40798-020-00243-0.
Replication studies are essential for identifying credible associations between alleles and phenotypes. Validation of genotype-phenotype associations in the sports and exercise field is rare. An initial genetic association study suggested that rs1049305 (C > G) in the 3' untranslated region (3'UTR) of the aquaporin-1 (AQP1) gene was associated with marathon running (MR) performance level in Hispanic males. To validate this finding, we conducted a replication analysis in an independent case-control sample of Hispanic male marathon runners (n = 1430; cases n = 713 and controls n = 717). A meta-analysis was utilized to test the extent of the association between the initial results and the present report. It also provided to test the heterogeneity (variation) between the two studies.
The replication study showed a statistically significant (p ≤ 0.05) association between rs1049305 (C > G) of the AQP1 gene and MR performance level. Association test results using a fixed effect model for the combined, original study and the present report, yielded an odds ratio = 1.28, 95% confidence interval = 1.13-1.45, p = 0.0001. The extent of the measures of heterogeneity was Tau-squared = 0, H statistic = 1, I statistic = 0, and Cochran's Q test (Q = 0.29; p value 0.59), indicated the variation between studies were due to chance and not to differences in heterogeneity between the two studies. Within the limitations of the present replication, contrast of two studies and its effects on meta-analysis, the findings were robust.
This study successfully replicated the results of Martínez et al. (Med Sportiva 13:251-5, 2009). The meta-analysis provided further epidemiological credibility for the hypothesis of association between the DNA rs1049305 (C > G) variation in the 3'UTR of the AQP1 gene and MR running performance level in Hispanics male marathon runners. It is not precluded that a linked DNA structure in the surrounding molecular neighborhood could be of influence by been part of the overly complex phenotype of MR performance level.
重复研究对于确定等位基因与表型之间可靠的关联至关重要。在体育和运动领域，基因型 - 表型关联的验证很少见。一项初步的基因关联研究表明，水通道蛋白 -1（AQP1）基因3'非翻译区（3'UTR）中的rs1049305（C>G）与西班牙裔男性的马拉松跑（MR）成绩水平相关。为了验证这一发现，我们在一个独立的西班牙裔男性马拉松跑者病例对照样本（n = 1430；病例n = 713，对照n = 717）中进行了重复分析。采用荟萃分析来检验初始结果与本报告之间关联的程度。它还用于检验两项研究之间的异质性（差异）。
重复研究表明，AQP1基因的rs1049305（C>G）与MR成绩水平之间存在统计学显著关联（p≤0.05）。对合并的原始研究和本报告使用固定效应模型的关联检验结果显示，优势比 = 1.28，95%置信区间 = 1.13 - 1.45，p = 0.0001。异质性测量程度为：Tau平方 = 0，H统计量 = 1，I统计量 = 0，Cochran's Q检验（Q = 0.29；p值0.59），表明研究之间的差异是由于偶然因素，而非两项研究之间的异质性差异。在本重复研究、两项研究的对比及其对荟萃分析的影响的局限性范围内，研究结果是可靠的。
本研究成功重复了Martínez等人（《Med Sportiva》13:251 - 5，2009）的结果。荟萃分析为AQP1基因3'UTR中DNA rs1049305（C>G）变异与西班牙裔男性马拉松跑者MR成绩水平之间的关联假说提供了进一步的流行病学可信度。不排除周围分子邻域中的连锁DNA结构可能作为MR成绩水平过于复杂表型的一部分而产生影响。
